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JAK-STAT 通路成分与前列腺癌患者预后的相关性分析。

Correlation analysis of JAK-STAT pathway components on prognosis of patients with prostate cancer.

机构信息

China-America Cancer Research Institute of Guangdong Medical College, Dongguan, People's Republic of China.

出版信息

Pathol Oncol Res. 2012 Jan;18(1):17-23. doi: 10.1007/s12253-011-9410-y. Epub 2011 Jun 18.

DOI:10.1007/s12253-011-9410-y
PMID:21681602
Abstract

Janus kinases (JAK)/signal transducers and activator of transcription (STAT) pathway is activated constitutively in prostate cancer (PCa). Despite previous reports implying a role of this pathway in the development of clinical hormone-refractory PCa, the correlation of pathway members with the clinicopathologic features and prognosis of patients with PCa has not been elucidated. To address this problem, pJAK-1(Tyr1022/1023) and pSTAT-3(Tyr705) were evaluated by immunostaining in needle biopsies of the prostate from 202 PCa patients treated by definitive therapy (105 cases) or hormonal therapy (97 cases). The correlation of two protein expression with the clinicopathologic features and the prognosis of PCa were subsequently assessed. The expression levels of pJAK-1(Tyr1022/1023) and pSTAT-3(Tyr705) were both positively correlated with Gleason score and clinical stage of patients with PCa. Their expression was also significantly higher in patients with biochemical (prostate-specific antigen, PSA) failure than that in those with no PSA failure (both P < 0.001). In all patients, the recurrence-free survival (RFS) rates were significantly higher in those with low pJAK-1(Tyr1022/1023) and pSTAT-3(Tyr705) expression than that in those with high expression (both P < 0.001). Moreover, for patients treated by definitive or hormonal therapy, the RFS rates in those with lower pJAK-1(Tyr1022/1023) (P < 0.001 and 0.012, respectively) and pSTAT-3(Tyr705) expression (P < 0.001 and 0.015, respectively) were significantly higher than in those with higher expression. Cox multivariate analysis showed that the expression levels of pJAK-1(Tyr1022/1023) (P = 0.002) and pSTAT-3(Tyr705) (P = 0.005) were prognostic factors for PCa in addition to extraprostatic extension (P = 0.026) and Gleason score (P = 0.018). The results of pJAK-1(Tyr1022/1023) and pSTAT-3(Tyr705) immunostainings in needle-biopsy specimens are prognostic factors for PCa.

摘要

Janus 激酶(JAK)/信号转导和转录激活因子(STAT)通路在前列腺癌(PCa)中持续激活。尽管先前的报告暗示该通路在临床激素难治性 PCa 的发展中起作用,但通路成员与 PCa 患者的临床病理特征和预后的相关性尚未阐明。为了解决这个问题,我们通过免疫染色评估了 202 例接受确定性治疗(105 例)或激素治疗(97 例)的前列腺癌患者的前列腺针吸活检组织中的 pJAK-1(Tyr1022/1023)和 pSTAT-3(Tyr705)。随后评估了两种蛋白表达与 PCa 的临床病理特征和预后的相关性。pJAK-1(Tyr1022/1023)和 pSTAT-3(Tyr705)的表达水平均与 PCa 患者的 Gleason 评分和临床分期呈正相关。在生化(前列腺特异性抗原,PSA)失败的患者中,其表达也明显高于 PSA 无失败的患者(均 P < 0.001)。在所有患者中,低表达 pJAK-1(Tyr1022/1023)和 pSTAT-3(Tyr705)的患者的无复发生存率(RFS)明显高于高表达的患者(均 P < 0.001)。此外,对于接受确定性或激素治疗的患者,低表达 pJAK-1(Tyr1022/1023)(P < 0.001 和 0.012)和 pSTAT-3(Tyr705)(P < 0.001 和 0.015)的患者的 RFS 率明显高于高表达的患者。Cox 多因素分析显示,除了前列腺外扩展(P = 0.026)和 Gleason 评分(P = 0.018)外,pJAK-1(Tyr1022/1023)(P = 0.002)和 pSTAT-3(Tyr705)(P = 0.005)的表达水平也是 PCa 的预后因素。针吸活检标本中 pJAK-1(Tyr1022/1023)和 pSTAT-3(Tyr705)免疫染色的结果是 PCa 的预后因素。

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